Prenatal diagnosis of Pallister-Killian syndrome using cord blood samples

Abstract

Background Pallister-Killian syndrome (PKS) (OMIM:#601803) is a rare sporadic genetic disorder characterized by multi-malformations which is caused by the presence of the extra isochromosome 12p. PKS is featured by the tissue-limited mosaicism of the isochromosome 12p [i(12p)]. There were a wide spectrum of prenatal ultrasound findings of PKS, which made it difficult to be found in first or second trimester. Polyhydramnios, diaphragmatic hernia, and rhizomelic limb shortening were the most common prenatal ultrasound abnormalities in PKS. This study retrospectively analyzed the ultrasound findings and molecular cytogenetic results of four PKS fetuses diagnosed by using cord blood samples. Results The ultrasound anomalies of four PKS fetuses are described as follows: fetal macrosomia, cerebral ventriculomegaly, increased NT thickness, rhizomelic limbs shortening, polyhydramnios. Biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL) measurements were above the mean in three fetuses,while one fetus showed rhizomelic limbs shortening. Combined with this study and previous literature, polyhydramnios was the most frequent anomaly observed in prenatal ultrasound examination of PKS, which accounted for 48% (94/194). Fetal macrosomia was present in 15% (29/194), cerebral ventriculomegaly in 13% (25/194), thickened nuchal fold in 9% (18/194), rhizomelic limbs shortening in 26% (51/194). I(12p) was found in the karyotype analysis of cultured cord blood lymphocytes and the mosaic ratios ranged from 2 to 5%. Single nucleotide polymorphisms array (SNP-array) results suggested that the whole short arm of chromosome 12 was duplicated with 2~3 copies. Fluorescence in situ hybridization (FISH) was performed to confirm the results of karyotype and SNP-array. Conclusions In case non-specific indicators such as fetal macrosomia, polyhydramnios and rhizomelic limbs shortening are observed meanwhile in prenatal ultrasound, targeted detection of PKS should be considered. In the prenatal diagnosis of PKS, the combination of SNP-array and FISH with conventional karyotype are the key to seek i(12p) and for precise diagnosis.

Prenatal diagnosis of Pallister‐Killian syndrome and literature review

“…Both cytogenetic and SNP array results of foetus 2 revealed non‐mosaicism PKS; however, the ultrasound only showed NT thickening. It may be related to the gestational age of the ultrasound test as more ultrasound abnormalities appear with increasing gestational age, 3,34 similar to foetus 1 and foetus 4 in our study. With regard to the next pregnancy, the risk of chromosomal abnormalities was primarily associated with advanced age rather than PKS pregnancy history.…”

Structural carcinoma overall process: a systematic review

“…Abnormalities have been found in the short arm of chromosome 12. The isochromosome I (12)p or a deletion in 12pa germ cell chromosomal marker -was observed in 25% of patients with poorly differentiated carcinoma and predominant lymph nodal disease [32][33][34]. Chromosomal instability (aneuploidy) was found in 70% of patients with metastatic adenocarcinoma or undifferentiated carcinoma [35,36].…”

Diagnóstico Pré-Natal Da Síndrome De Pallister-Killian: Uma Revisão Integrativa

“…Wang et al 9 Achados ultrassonográficos de um estudo retrospectivo e resultados citogenéticos moleculares.…”

“…O presente trabalho justifica-se nesse ponto devido às implicações sérias tanto em relação ao diagnóstico, a patologia, comorbidades dos pacientes, quanto para o aconselhamento de pacientes e familiares 9 .…”